PROJECT SUMMARY/ ABSTRACT (RESEARCH PROJECT) Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms (LUTS) in men. Given the clinical and pathological heterogeneity in disease presentation, it is likely that BPH represents a molecularly heterogeneous disease. Furthermore, distinct molecular subtypes of BPH are likely driven by different pathways, encompassing epigenetic regulation, cell signaling, stromal-epithelial interactions and other causes. Identification of these BPH subtypes and drivers will lead to novel targets for treatment. To address this clinical challenge in LUTS through the Center's vision of precision medicine, the Scientific Research Project has two broad aims. The first aim is to apply sequence-based transcriptional profiling to define a new molecular classification of BPH, identify BPH biomarkers and associated microbes, and discover disease drivers and therapeutic targets. The second aim is to develop novel BPH cell culture models using conditionally reprogrammed cell (CRC) technology, and to investigate putative known and novel BPH drivers. Findings will support follow-on translational studies of BPH and LUTS, and provide key resources in minable data and BPH cell models. These studies bring together leaders from fields outside of Urology to apply innovative methods and approaches to problems in LUTS.